Pharmacologic MRI in Cocaine-addiction
Two pharmacologic probes will be administered to both healthy controls and cocaine-addicted participants in three different sessions. All probes have previously used by our laboratory: ondansetron [a serotonin 3 (5HT3) receptor antagonist] and lidocaine (a sodium channel blocker). Pharmacologic fMRI (phMRI) measures will be obtained prior to and following administration, including both arterial spin labeling (ASL) and functional connectivity measures (fcMRI).
Up to ten cocaine-addicted and ten healthy control subjects will be studied. Assessment will include history and physical, diagnostic interview, routine labs, and EKG. Cocaine addicted-subjects may be inpatient or outpatient but must have negative urine drug screens on the day each study session. Sessions will be separated by at least 48 hours to minimize pharmacologic overlap between each study. When possible, all studies will be performed in the same week. Study order will be pseudo-randomized (i.e. order will be determined beforehand to assure that study order is different for the 6 subjects in each group).
Upon arrival to the medical center for each study session, a urine drug screen will be obtained from each subject and a pregnancy test from all female subjects. A Brief Symptom Inventory will also be administered. An intravenous catheter will then be inserted into the forearm and subjects will be placed in the MRI. In the first session, MPRAGE T1 anatomic scans will be obtained at the beginning of scan sequence for registration. In the other sessions, only anatomic pilot scans will be obtained. These scans will be co-registered with the previous MPRAGE. Anatomic scans in each session will be followed by baseline fcMRI (5 min) and ASL (5 min) scans. These scans will be immediately followed by the infusion of medication.
Ondansetron: Ondansetron (0.15 mg/kg) will be administered through the IV line over 15 min at a constant rate of infusion. ASL will be obtained during the infusion and for an addition 15 min, followed by 5 min of fcMRI. The total session will last approximately 90 minutes. This is the same paradigm as used for our SPECT paradigm (i.e. 15 min ondansetron infusion followed 15 min later by SPECT).
Lidocaine: Lidocaine will be administered as a 2mg/kg initial bolus over 5 minutes followed by a continuous intravenous infusion of lidocaine at a rate of 2mg/kg/hour for 55 min (60 min total infusion). ASL will be obtained for 55 min, followed by 5 min of fcMRI. The total session will last approximately 90 minutes. In our previous studies with lidocaine, lidocaine was administered as a bolus over one min (0.5 mg/kg). However, the proposed dose is consistent with its use in the treatment of chronic pain.
Inclusion Criteria: Participants can be male or female and between the ages of 21-64 years old. Patients of any race will be eligible for this study. Participants must meet DSM-IV criteria for cocaine abuse or dependence and must identify cocaine as their present primary drug of use. Patients must have used cocaine within the previous 4 weeks (by patient history) and abstinent at least 1 week. They may be attending inpatient or outpatient treatment at the Dallas VAMC or Homeward Bound Inc. or non-treatment seeking.
Inclusion criteria: Healthy controls will be 21-64 years old. Healthy controls of any race will be used for this study.